510(k) substantial equivalence …5- nitroaniline in acidic medium. varying bilirubin levels will...

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510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY

ASSAY AND INSTRUMENT COMBINATION TEMPLATE

A. 510(k) Number:

k160062

B. Purpose for Submission:

New device

C. Measurand:

Measurement of the following in urine samples: glucose, protein, bilirubin, urobilinogen, pH, blood, ketones, nitrite, leukocytes, and specific gravity.

D. Type of Test:

Qualitative and semi-quantitative urinalysis

E. Applicant:

Arkray, Inc.

F. Proprietary and Established Names:

AUTION ELEVEN Semi-Automated Urinalysis System

G. Regulatory Information:

1. Regulation section:

Name Regulation Product Code

Device Class

Urinary Glucose (non-quantitative) test system 21 CFR §862.1340 JIL II

Occult blood test 21 CFR §864.6550 JIO II Urinary urobilinogen (non-quantitative) test system 21 CFR §862.1785 CDM I

Urinary pH (non-quantitative) test system

21 CFR §862.1550 CEN I Ketones (non-quantitative) test system 21 CFR §862.1435 JIN I

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Name Regulation ProductCode

Device Class

Urinary protein or albumin (non-quantitative) test system 21 CFR §862.1645 JIR I

Urinary bilirubin and its conjugates (non-quantitative) test system 21 CFR §862.1115 JJB I

Nitrite (non-quantitative) test system 21 CFR §862.1510 JMT I Leukocyte peroxidase test 21 CFR §864.7675 LJX I Specific Gravity 21 CFR §862.2800 JRE I Automated Urinalysis System 21 CFR §862.2900 KQO I

2. Panel: Chemistry (75) Hematology (81)

H. Intended Use:

1. Intended use(s):

See indications for use statements below.

2. Indication(s) for use:

The AUTION ELEVEN Semi-Automated Urinalysis System provides a qualitative and semi-quantitative measurements for glucose, protein, bilirubin, urobilinogen, pH, blood, ketones, nitrites, leukocytes, specific gravity and color tone in urine specimens. The system is intended for in vitro diagnostic use in screening patient populations found in clinical laboratories.

The AUTION ELEVEN Semi-Automated Urinalysis System consists of the following:

• AUTION ELEVEN model AE-4022 Urine Analyzer (device component) • AUTION Sticks 10EA Test Strips (reagent component)

3. Special conditions for use statement(s):

For prescription use only.

4. Special instrument requirements:

AUTION ELEVEN AE-4022 Semi-automatic Urine Analyzer

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I. Device Description:


The AUTION ELEVEN AE-4022 Semi-automatic Urine Analyzer is a semi-automated urine chemistry analyzer intended for use with the AUTION Sticks 10EA multi-analyte test strips for the qualitative and semi-quantitative measurement of the following parameters: glucose, protein, bilirubin, urobilinogen, pH, blood, ketones, nitrites, leukocytes, specific gravity.

The instrument is intended for professional use as an in-vitro diagnostic screening test in clinical laboratories.

Provided with the analyzer are an AUTION Check Strip set. These are strips used as a quality control check of the instrument’s reflectance measurement system. The check strip bottle contains two gray and two white check strips. For the QC measurement, one test strip of each type is used, and the results compared to pre-defined reflectance levels at four wavelengths.

A hand held barcode reader is optionally available with the instrument to enter a patient ID.

AUTION Sticks 10EA

The AUTION Sticks 10EA are multi-analyte test strips intended for use with the AUTION ELEVEN AE-4022 Semi-automatic Urine Analyzer. The test strips comprise a plastic strip with 10 reagent pads impregnated with chemistries specific for the determination of each analyte. The test strips are sold separately with 100 sticks per bottle.

J. Substantial Equivalence Information:

1. Predicate device name(s): AUTION MAX AX-4030 Urinalysis System

2. Predicate 510(k) number(s):

k093098

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3. Comparison with predicate:

Similarities

Item

Subject Device k160062


Predicate Device k093098

AUTION MAX AX-4030 Urinalysis System

Intended Use Semi-automated urine chemistry analyzer for the in vitro measurement of urine chemistry analytes.

Same

Measurands Glucose, Protein, Bilirubin, Urobilinogen, pH, Blood, Ketones, Nitrites, Leukocytes, Specific Gravity

Same

Sample Type Human urine Same

Data type Qualitative and semi-quantitative

Same

Measurement principle

Reflectance Same

Assay measurement wavelengths

Each assay is measured at two wavelengths from 565, 635, and 760 nm; except blood which is measured at 635 nm.

Same

Differences

Item

Subject Device k160062


Predicate Device k093098

AUTION MAX AX-4030 Urinalysis System

Test Strip AUTION Sticks 10EA

10 pads for each analytes.

Uses a blank pad for urine color correction.

AUTION Sticks 9EB 9 pads for each analytes, except for specific gravity which is measured by a refractive index method. Uses blank pad for urine color correction.

Assay reaction time, and control

60 seconds

Audio alarm assisted, manual control

Same Automated

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K. Standard/Guidance Document Referenced (if applicable):

· EC ISO 14971: 2007 second edition, Medical devices-Application of risk management to medical devices.

· Clinical and Laboratory Standards Institute.(2014). EP05-A3 Vol34 No.13 Evaluation of Precision of Quantitative Measurement Procedures.

· Clinical and Laboratory Standards Institute.(2003). EP06-A Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach.

· Clinical and Laboratory Standards Institute.(2005). EP07-A2 Interference Testing Clinical Chemistry.

· Clinical and Laboratory Standards Institute.(2010). EP09-A2-JR Method Comparison and Bias Estimation Using Patient Samples.

· Clinical and Laboratory Standards Institute. (2009). GP-16-A2 21 No.19 Urinalysis; Approved Guideline – Third Edition.

· Clinical and Laboratory Standards Institute. (2012). EP17-A2 Vol32 No.8 Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline- Second Edition.

L. Test Principle:

The AUTION ELEVEN AE-4022 Semi-automatic Urine Analyzer device uses combinations of 4 light emitting diodes to measure the reflectance of the reagent pads of the AUTION 10EA Stick test strips. Two wavelengths are used for the reflectance determination of each analyte, except blood which uses a single wavelength. The percent reflectance received by the optical sensor for each analyte on the test strip is then used to calculate a semi-quantitative value and a qualitative value.

The AUTION ELEVEN AE-4022 Semi-automatic Urine Analyzer also measures urine color tone. This is done by measuring the reflectance of a blank pad on the AUTION 10EA Stick. The concentration for each analyte is corrected for urine color tone, so that the urine color does not interfere with measurement.

Assay Principles of the AUTION 10EA Stick:

Glucose: Based on a double sequential enzyme reaction. Glucose oxidase catalyzes the formation of gluconic acid and hydrogen peroxide from the oxidation of glucose. A second enzyme, peroxidase, catalyzes the oxidative coupling of 4-amino-antipyrine and 1-Naphthol-3-6-disulfonic acid by hydrogen peroxide to form a Quinone imine purple color.

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Protein: Based on the protein-error-of-indicators reaction. At a constant pH, the presence of protein causes a change in the color of the indicator to a cyan color.

Bilirubin: The test is based on azo-coupling reaction of bilirubin with diazotized 2-methyl-5- nitroaniline in acidic medium. Varying bilirubin levels will produce a reddish brown color.

Urobilinogen: The test is based on azo-coupling reaction of Urobilinogen with diazotized 3,3’-dimethyloxy-4,4’-biphenyl bis-diazonium tetrafluoroborate in acidic medium. Varying Urobilinogen levels will produce a reddish brown color.

pH: Based on a mixed indicator principle that gives a broad range of colors (yellow to cyan) covering the entire urinary pH range.

Specific Gravity: Cation extraction.

Blood: Based on the peroxidase-like activity of hemoglobin, which catalyzes the reaction of Cumene hydroperoxide and 3,3,5,5’- tetramethylbenzidine to form a cyan color.

Ketones: Legal reaction. Based on the reaction of sodium nitroprusside with acetoacetic acid to form a purple complex.

Nitrites: Griess reaction. Nitrite reacts with sulfanilamide, followed by a diazo-coupling reaction to from a pink colored product.

Leukocytes: Granulocytic leukocytes contain esterases that catalyze the hydrolysis of 3-(N-Toluenesulfonyl-L-alanyloxy) indole (TAI) to from indoxyl, which further reacts with 2-Methoxy-4-(N-morpholino) benzenediazonium (MMB) to form a purple product.

M. Performance Characteristics (if/when applicable):

1. Analytical performance:

a. Precision/Reproducibility:

Precision studies were conducted using the Semi-Automated Urinalysis System consisting of the AUTION ELEVEN AE -4022 Semi-Automatic Urine Analyzer and the AUTION Sticks 10EA. The studies were performed at three clinical laboratory sites. At each site, the precision study was conducted by one operator using one instrument and one lots of test strips. For the precision studies, three samples were tested in duplicate in each run, two runs per day for 20 days for a total of 80 replicates for each site.

The samples were three levels of urine-based quality control material: negative, mid-level positive, and high-positive.

Within run (repeatability) and total imprecision (reproducibility) were calculated.

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The combined results for the three testing sites are summarized in the following tables:

Negative control: Analyte

Expected

result

REPEATABILITY (N=120)

REPRODUCIBILITY (N=240)

Exact Agreement

(%)

Within +/- 1 block

(%)

Exact Agreement

(%)

Within +/- 1 block

(%)

Glucose NEG [-] 100% (120/120)

100% (120/120)

100% (240/240)

100% (240/240)

Protein NEG [-] 100% (120/120)

100% (120/120)

100% (240/240)

100% (240/240)

Bilirubin NEG [-] 100% (120/120)

100% (120/120)

100% (240/240)

100% (240/240)

Urobilinogen Normal 100% (120/120)

100% (120/120)

100% (240/240)

100% (240/240)

pH 5.0 100% (120/120)

100% (120/120)

100% (240/240)

100% (240/240)

Blood NEG [-] 100% (120/120)

100% (120/120)

100% (240/240)

100% (240/240)

Ketones NEG [-] 100% (120/120)

100% (120/120)

100% (240/240)

100% (240/240)

Nitrite NEG [-] 100% (120/120)

100% (120/120)

100% (240/240)

100% (240/240)

Leukocytes NEG [-] 100% (120/120)

100% (120/120)

100% (240/240)

100% (240/240)

Specific Gravity < 1.005 100% (120/120)

100% (120/120)

100% (240/240)

100% (240/240)

Mid-level positive control: Analyte

Expected

result



Exact Agreement

(%)

Within +/- 1 block

(%)

Exact Agreement

(%)

Within +/- 1 block

(%)

Glucose 2+ 100% (120/120)

100% (120/120)

100% (240/240)

100% (240/240)

Protein 1+ 100% (120/120)

100% (120/120)

100% (240/240)

100% (240/240)

Bilirubin 2+ 100% (120/120)

100% (120/120)

100% (240/240)

100% (240/240)

Urobilinogen 2+ 98% (118/120)

100% (120/120)

99% (240/240)

100% (240/240)

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Analyte Expected result



Exact Agreement

(%)

Within +/-1 block

(%)

Exact Agreement

(%)

Within +/-1 block

(%)

pH 7.0 95% (114/120)

100% (120/120)

97% (233/240)

100% (240/240)

Blood 2+ 100% (120/120)

100% (120/120)

100% (240/240)

100% (240/240)

Ketones 2+ 100% (120/120)

100% (120/120)

100% (240/240)

100% (240/240)

Nitrite 2+ 100% (120/120)

100% (120/120)

100% (240/240)

100% (240/240)

Leukocytes 500 Leu/µL 100% (120/120)

100% (120/120)

100% (240/240)

100% (240/240)

Specific Gravity 1.020 98% (118/120)

100% (120/120)

99% (238/240)

100% (240/240)

High-positive control: Analyte

Expected

result



Exact Agreement

(%)

Within +/- 1 block

(%)

Exact Agreement

(%)

Within +/- 1 block

(%)

Glucose 3+ 93% (112/120)

100% (120/120)

97% (232/240)

100% (240/240)

Protein 3+ 100% (120/120)

100% (120/120)

100% (240/240)

100% (240/240)

Bilirubin 4+ 96% (115/120)

100% (120/120)

98% (235/240)

100% (240/240)

Urobilinogen 4+ 100% (120/120)

100% (120/120)

100% (240/240)

100% (240/240)

pH 8.0 98% (118/120)

100% (120/120)

99% (238/240)

100% (240/240)

Blood 3+ 98% (118/120)

100% (120/120)

99% (238/240)

100% (240/240)

Ketones 4+ 88% (106/120)

100% (120/120)

94% (226/240)

100% (240/240)

Nitrite 2+ 100% (120/120)

100% (120/120)

100% (240/240)

100% (240/240)

Leukocytes 500 Leu/µL 100% (120/120)

100% (120/120)

100% (240/240)

100% (240/240)

Specific Gravity 1.025 88% (106/120)

100% (120/120)

91% (218/240)

100% (240/240)

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b. Linearity/assay reportable range:

A study was conducted to evaluate the reportable range for each analyte of the AUTION ELEVEN Semi-Automated Urinalysis System. The reportable range was evaluated by measuring samples with known concentrations of each analyte covering all measurement color block ranks.

Samples were measured using 3 lots of test strips in replicates of 7 for a total of 21 measurements per sample. The results are summarized below:

Analyte Level (mg/dL) Exact match ±1 color block match

Glucose

0 (-) 100% (21/21) 100% (21/21) 45 (±) 90.5% (19/21) 100% (21/21) 85 (1+) 100% (21/21) 100% (21/21) 170 (2+) 100% (21/21) 100% (21/21) 340 (3+) 100% (21/21) 100% (21/21) 2700 (4+) 100% (21/21) 100% (21/21)


Protein

0 (-) 100% (21/21) 100% (21/21) 15 (±) 100% (21/21) 100% (21/21) 30 (1+) 100% (21/21) 100% (21/21) 120 (2+) 100% (21/21) 100% (21/21) 480 (3+) 100% (21/21) 100% (21/21) 1000 (4+) 100% (21/21) 100% (21/21)


Bilirubin

0 (-) 100% (21/21) 100% (21/21) 1.5 (1+) 100% (21/21) 100% (21/21) 3 (2+) 100% (21/21) 100% (21/21) 6 (3+) 100% (21/21) 100% (21/21) 12 (4+) 100% (21/21) 100% (21/21)


Urobilinogen

Normal 100% (21/21) 100% (21/21) 3 (1+) 100% (21/21) 100% (21/21) 5 (2+) 100% (21/21) 100% (21/21) 10 (3+) 95.2% (20/21) 100% (21/21) 20 (4+) 100% (21/21) 100% (21/21)

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Analyte Level Exact match ±1 color block match

pH

5.0 100% (21/21) 100% (21/21) 5.5 100% (21/21) 100% (21/21) 6.0 100% (21/21) 100% (21/21) 6.5 100% (21/21) 100% (21/21) 7.0 95.2% (20/21) 100% (21/21) 7.5 100% (21/21) 100% (21/21) 8.0 100% (21/21) 100% (21/21) 8.4 95.2% (20/21) 100% (21/21) 9.0 100% (21/21) 100% (21/21)

Analyte Level Exact match ±1 color block match

Specific gravity

1.005 100% (21/21) 100% (21/21) 1.010 100% (21/21) 100% (21/21) 1.015 95.2% (20/21) 100% (21/21) 1.020 90.5% (19/21) 100% (21/21) 1.025 100% (21/21) 100% (21/21) 1.030 100% (21/21) 100% (21/21)


Blood

0 (-) 100% (21/21) 100% (21/21) 0.03(±) 100% (21/21) 100% (21/21)

0.08 (1+) 100% (21/21) 100% (21/21) 0.6 (2+) 95.2% (20/21) 100% (21/21) 1.3 (3+) 100% (21/21) 100% (21/21)


Ketone

0 (-) 100% (21/21) 100% (21/21) 5 (±) 100% (21/21) 100% (21/21)

15 (1+) 100% (21/21) 100% (21/21) 60 (2+) 100% (21/21) 100% (21/21) 120 (3+) 90.5% (19/21) 100% (21/21) 240 (4+) 100% (21/21) 100% (21/21)

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Nitrite 0 (-) 100% (21/21) 100% (21/21)

0.1 (1+) 100% (21/21) 100% (21/21) 0.8 (2+) 100% (21/21) 100% (21/21)

Analyte Level (Leu/µL) Exact match ±1 color block match

Leukocyte

0 (-) 100% (21/21) 100% (21/21) 25 100% (21/21) 100% (21/21) 75 95.2% (20/21) 100% (21/21) 250 100% (21/21) 100% (21/21) 520 100% (21/21) 100% (21/21)

The reportable ranges of each analyte of the AUTION ELEVEN Semi-Automated Urinalysis System are summarized below:

Analyte Reportable range

Glucose Qualitative: negative to 4+ Semi-quantitative: negative to 1000 mg/dL

Protein Qualitative: negative to 4+ Semi-quantitative: negative to 1000 mg/dL

Bilirubin Qualitative: negative to 4+ Semi-quantitative: negative to 14 mg/dL

Urobilinogen Qualitative: normal to 4+ Semi-quantitative: normal to 16 mg/dL

Blood Qualitative: negative to 3+ Semi-quantitative: negative to 1.0 mg/dL

Ketones Qualitative: negative to 4+ Semi-quantitative: negative to 150 mg/dL

Nitrite Qualitative: negative to 2+ pH Measured value: 5.0 to 9.0

Specific gravity Measured value: <1.005 - >1.030

Leukocytes Semi-quantitative: negative to 500 mg/dL

c. Traceability, Stability, Expected values (controls, calibrators, or methods):

Traceability:

Each assay of the AUTION ELEVEN Semi-Automated Urinalysis System is traceable to the following standards:

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Analyte Reference Method Standardization Glucose GOD electrometry D‐Glucose Protein Pyrogallol red method Human albumin

Bilirubin Shibata method *Zn‐ Azobilirubin method Bilirubin IV

Urobilinogen Watson method Phenolsulfon‐phthalein pH pH Meter Calibrator

Specific Gravity Refractometer Sodium chloride Blood Reference material gravimetry Human hemoglobin

Ketones Reference material gravimetry Lithium acetoacetate Nitrite Reference material gravimetry Sodium nitrite

Leukocyte Fuchs rosenthal counting Human leukocytes

Shelf life stability of AUTION Sticks 10EA:

Stability studies were performed to assess the shelf life (closed bottle) stability for the AUTION Stick 10EA urine strips used on the AUTION ELEVEN AE-4022 Semi-automatic Urine Analyzer. The protocol and acceptance criteria were reviewed and found sufficient. The stability studies supports the claim that AUTION Sticks 10EA, unopened, are stable for 2 years from date of manufacture when stored within temperature range of 34 to 86°F.

Open bottle stability of AUTION Sticks 10EA:

Open bottle stability studies were performed on the AUTION Stick 10EA urine strips used on the AUTION ELEVEN AE-4022 Semi-automatic Urine Analyzer. The protocol and acceptance criteria were reviewed and found sufficient. Based on the studies, once opened, the test strips are stable for 31 days when stored from 34 to 86 °F.

Transport (High Temperature) stability for AUTION Sticks 10EA:

High temperature stability studies were performed on the AUTION Stick 10EA urine strips to establish stability performance at high temperatures that may be experienced during product shipment. The protocol and acceptance criteria were reviewed and found sufficient. Based on the studies, the test sticks may be stored or transported in closed bottle containers at a temperature up to 50°C for 1 week without deterioration.

d. Detection limit:

Study 1: A detection limit study was conducted on each analyte of the AUTION ELEVEN Semi-Automated Urinalysis System to determine the concentration which changed the rank measurement block from negative to the next level rank measurement block (rank 1 to rank 2).

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Samples were prepared by spiking analyte into negative pooled urine. Each pool was spiked with the target analyte concentration, plus a concentration on each side of the target in order to determine the sensitivity concentration. Each samples was analyzed in replicates of 5 using 3 strip lots, for a total of n=30 results. The analytical sensitivity for each rank measurement color block is defined as the lowest concentration at which ≥50% of the test results are positive between the negative color block, and the first positive (1+) or trace (±) color block. The results are summarized in the following table:

Analyte Sensitivity % Sensitivity Glucose 30 mg/dL 100 Protein 10 mg/dL 100

Bilirubin 0.5 mg/dL 50 Urobilinogen 2 mg/dL 100

Blood 0.023 mg/dL 100 Ketones 3 mg/dL 73 Nitrites 0.08 mg/dL 50

Leukocytes 25 Leu/uL 100

Study 2: A sensitivity study was conducted to demonstrate the cut-off concentration between the qualitative measurement blocks for each analyte of the AUTION Stick 10EA. The low cut-off concentration for each measurement block is defined as the lowest concentration at which ≥ 50% of the test results are positive for the greater color block. Samples were prepared by spiking analyte into negative pooled urine pool. Each pool was spiked with the target analyte concentration. Additionally, a sample was prepared at a slightly lower concentration than the target concentration. Each sample was created twice, using 2 urine pools, and tested in replicates of 5 on each pool. Each urine pool was tested with 3 lots of reagent strips for a total of 30 replicates per sample.

The low cut-off concentrations for each qualitative measurement rank of each analyte are summarized in the table below.

Glucose

Block output Low concentration cut-off (mg/dL) Sensitivity

1+ 60 100% 2+ 125 100% 3+ 250 100% 4+ 750 87%

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Protein


1+ 25 63% 2+ 85 100% 3+ 250 100% 4+ 800 97%

Bilirubin


2+ 1.9 53% 3+ 5.3 87% 4+ 12 100%

Urobilinogen


2+ 3.5 50% 3+ 6.5 100% 4+ 14 100%

pH Block output Low cut-off Sensitivity

5.5 5.3 100% 6.0 5.8 100% 6.5 6.3 87% 7.0 6.8 100% 7.5 7.3 87% 8.0 7.8 97% 8.5 8.3 50% 9.0 8.9 50%

Specific Gravity Block output Low cut-off Sensitivity

1.010 1.008 53% 1.015 1.013 100% 1.020 1.019 100% 1.025 1.023 97% 1.030 1.028 83%

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Blood


1+ 0.05 97% 2+ 0.18 87% 3+ 0.9 50%

Ketones


1+ 7.5 100% 2+ 30 100% 3+ 70 87% 4+ 130 100%

Nitrites


2+ 0.3 100%

Leukocytes

Block output Low concentration

cut-off (Leukocytes/µL)

Sensitivity

75 50 100% 250 180 100% 500 390 87%

e. Analytical specificity:

Analytical specificity studies were performed to assess the interfering effect of various substances to the AUTION ELEVEN Semi-Automated Urinalysis System.

Urine samples were prepared at one concentration for each analyte. A high positive sample was prepared by spiking each analyte into pooled negative urine. The sample pools were spiked with potential interfering substances at the concentrations listed below:

Concentrations tested Substance Low Middle Positive Units Acetoacetate 60 - 150 mg/dL Albumin 300 - 1000 mg/dL Ammonium chloride 100 - 400 mg/dL Ascorbic acid 50 - 200 mg/dL

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Concentrations testedSubstance Low Middle Positive UnitsBilirubin 4 - 16 mg/dL Calcium chloride 40 - 160 mg/dL Citric acid 65 - 130 mg/dL Creatinine 300 - 600 mg/dL Fructose 100 - 300 mg/dL Galactose 100 - 300 mg/dL Glucose 200 500 2000 mg/dL Glycine 450 - 900 mg/dL Hemoglobin 0.3 - 50 mg/dL Potassium chloride 500 - 1000 mg/dL Lactose 100 - 300 mg/dL MESNA 50 - 200 mg/dL Sodium chloride 1000 - 2000 mg/dL Oxalic acid 20 - 70 mg/dL pH (Citric acid) pH (Sodium phosphate) 3, 4, 8, 9 n/a

Phenolphthalein 2 - 10 mg/dL Riboflavin 2 - 5 mg/dL Sodium acetate 300 - 1200 mg/dL Sodium bicarbonate 500 - 1000 mg/dL Sodium nitrate 0.5 - 10 mg/dL Sodium nitrite 0.5 - 2 mg/dL Sodium phosphate 500 - 1000 mg/dL Specific gravity (Sucrose) 1.010 - 1.030 n/a Tetracycline 20 - 100 mg/dL Urea 1000 - 3000 mg/dL

Each sample was measured on the instrument in replicates of 5. The mean reflectance was calculated for each sample type. To assess whether a substance caused significant interference, the %reflectance from samples with no interfering substance was compared against the mean %reflectance of the sample spiked with the interfering substance. Interference was determined based on the acceptance criteria stated below:

Negative Samples: If mean values are 1+ (75 for Leukocytes) or greater, interference is considered positive.

For pH and Specific gravity: If mean value is greater than +/-1 rank, there is significant interference.

Positive Samples: If sample results differ by greater than +/- 1 color block between samples containing the interfering substance and samples without it, interference will be considered positive.

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Additional testing was conducted on certain substances that showed significant interference at the highest level. The concentration of the interferent reduced until, the rank measurement block change was with +/- 1. This is given in the table below:

Analyte Substance Concentrations Glucose Ascorbic acid 0, 50, 100 mg/dL

Protein Hemoglobin 0, 20, 30 mg/dL Specific gravity Ammonium chloride 0, 200, 300 mg/dL pH 8 Ascorbic acid 0, 100, 300 mg/dL pH 8 Calcium chloride 0, 100, 130 mg/dL Urobilinogen Bilirubin 2, 3, 4 mg/dL Ketones MESNA 5, 20, 30, 40, 50, 60 mg/dL Bilirubin Urobilinogen 4, 8, 16, 32 mg/dL

Based on the results of this testing the substance listed in the table below were found to significantly interfere.

Analyte Substances causing false negative

Substances causing false positive

Glucose Ascorbic acid (> 50 mg/dL) < pH 4 Protein Hemoglobin (> 20 mg/dL)

Bilirubin Urobilinogen (> 8 mg/dL) Urobilinogen Bilirubin (> 3 mg/dL)

pH

Specific gravity

Albumin (> 300 mg/dL); Ammonium chloride (> 200

mg/dL); < pH 4

Blood MESNA (> 50 mg/dL) Ketones MESNA (> 5 mg/dL) Nitrite

Leukocytes Albumin (> 300 mg/dL); Glucose (> 200 mg/dL);

< pH 4

Concentrations of the potentially interfering substances that will not have influence on the test results are shown below:

Substance Highest Concentration not affecting the test (mg/dL)

Acetoacetate 150 Albumin 300 Ammonium chloride 100 Ascorbic acid 50 Bilirubin 3

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Substance Highest Concentration not affecting the test (mg/dL)

Calcium chloride 160, except pH Citric acid 130, except pH Creatinine 600 Fructose 300 Galactose 300 Glucose 200 Glycine 900 Hemoglobin 20 Potassium chloride 1000 Lactose 300 MESNA 5 Sodium chloride 1000 Oxalic acid 20 Phenolphthalein 10 Riboflavin 5 Sodium acetate 1200 Sodium bicarbonate 1000, except pH Sodium nitrate 10 Sodium nitrite 2 Sodium phosphate 1000, except pH Tetracycline 100 Urea 3000

The labeling includes a list of the interfering substance and statement as shown below:

Analyte Interferent Concentration Result

Glucose Ascorbic acid > 50 mg/dL False negative

(-2 to -3 color block change)

pH < pH 4 False positive (+2 color block change)

Protein Hemoglobin > 20 mg/dL False positive (+2 color block change)

Bilirubin Urobilinogen > 8 mg/dL False positive (+1 color block change)

Urobilinogen Bilirubin > 3 mg/dL False positive (+1 color block change)

pH

Specific gravity

pH < pH 4 Elevated (+2 color block change)

Albumin > 300 mg/dL Elevated (+2 color block change)

Ammonium > 200 mg/dL Elevated

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Analyte Interferent Concentration Result chloride (+2 color block change)

Blood Substance that contain MESNA > 50 mg/dL False negative

(-2 color block change)

Ketones Substance that contain MESNA > 5 mg/dL

False positive (+2 to +5 color block

change) Nitrite

Leukocytes

Glucose > 200 mg/dL False negative (-2 color block change)

Albumin > 300 mg/dL False negative (-2 color block change)

pH < pH 4 False negative (-2 color block change)

The effect of pH The following tests were found to be affected by pH of 3 of lower: Glucose, Specific gravity, and Leukocytes.

The effect of Specific gravity No interference was found on the analytes due to urine specific gravity using sucrose as additive to change specific gravity.

Color tone detection and correction A study was conducted to verify that the system is insensitive to interference from red, brown, orange and green colored urine samples.

The samples were two levels of commercial control material (negative and high-positive); ThermoScientific MAS Controls 1 and 2. To the samples were spiked dyes to create the colors of red, orange, brown, and green. For reference, the control materials were spiked with water. No significant effect on color on the results was if the sample with added dye read with +/- 1 rank measurement block.

Based on the results, is no interference on measurement results due to variations in sample color tone.

Results for Low control: Analyte Reference Red Brown Orange Green Glucose negative negative negative negative negative Protein negative negative negative negative negative Bilirubin negative negative negative negative negative Urobilinogen 2+ 1+ 2+ 2+ 2+ pH 8.0 8.0 8.0 8.0 7.5 Specific gravity <1.005 <1.005 <1.005 <1.005 1.010

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Blood negative negative negative negative negative Ketones 2+ 2+ 2+ 2+ 2+ Nitrite negative negative negative negative negative Leukocytes 500 250 250 250 250 Color yellow red brown orange light green

Results for High control: Analyte Reference Red Brown Orange Green Glucose 2+ 2+ 2+ 2+ 2+ Protein 2+ 2+ 2+ 2+ 2+ Bilirubin 2+ 2+ 2+ 2+ 2+ Urobilinogen normal normal normal normal normal pH 6.5 6.5 6.5 6.5 6.0 Specific gravity 1.020 1.020 1.020 1.020 1.020 Blood 1+ 1+ 1+ 1+ 1+ Ketones negative negative negative negative negative Nitrite 2+ 1+ 2+ 2+ 2+ Leukocytes negative negative negative negative negative Color Dark yellow red brown orange green

f. Assay cut-off:

Not applicable.

2. Comparison studies:

a. Method comparison with predicate device:

Method comparison studies were conducted to evaluate the performance of the AUTION ELEVEN Semi-Automated Urinalysis System for the measurement of urine chemistry analytes. Results were compared to those from the predicate AUTION MAX AX-4030 Automated Urine Analyzer for all analytes except Specific Gravity. The AUTION JET AJ-4270 Urine Analyzer (k030600) was the comparator method for specific gravity.

Testing was performed at multiple sites by at least4 operators and using at least 4 instruments, and 3 different lots of test sticks. The urine samples for analysis were provided by either local hospitals or each site’s internal clinical laboratory. Specimens were single daily urine. These were refrigerated at 2-8°C within 2 hours of collection, and tested within 24 hours of collection. For testing, the samples were allowed to warm to room temperature (10 to 30°C) for 30 minutes, and were tested within 2 hours. In order to obtain the necessary range in concentration for each analyte, a small number of the samples were prepared by spiking analyte into urine. These samples constituted no more than 7% of the total.

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The data from each site was combined and are presented in concordance charts showing percentage of exact agreement and percentage agreement within ±1 color block agreement, as shown in the following tables.

Glucose REFERENCE: AX-4030 neg ± 1+ 2+ 3+ 4+

AE-

4022

neg 1845 4 0 0 0 0 ± 4 69 8 0 0 0

1+ 0 0 35 8 0 0 2+ 0 0 1 45 2 0 3+ 0 0 0 4 54 8 4+ 0 0 0 0 4 108

total 1849 73 44 57 60 116 exact match 99.8% 94.5% 79.6% 78.9% 90.0% 93.1%

within ±1 color block 100% 100% 100% 100% 100% 100%

Overall exact agreement = 98.0% Within +/- 1 block agreement = 100%

Protein REFERENCE: AX-4030 neg ± 1+ 2+ 3+ 4+

AE-

4022

neg 222 9 0 0 0 0 ± 24 118 11 0 0 0

1+ 0 13 98 3 0 0 2+ 0 0 9 27 2 0 3+ 0 0 0 3 11 0 4+ 0 0 0 0 3 10

total 246 140 118 33 16 10 exact match 90.2% 84.3% 83.0% 81.8% 68.8% 100%

within ±1 color

block 100% 100% 100% 100% 100% 100%

Overall exact agreement = 86% Within +/- 1 block agreement = 100%

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Bilirubin REFERENCE: AX-4030 neg 1+ 2+ 3+ 4+

AE-

4022

neg 2125 0 0 0 0 1+ 8 53 1 0 0 2+ 0 0 56 0 0 3+ 0 0 0 40 0 4+ 0 0 0 3 37

total 2133 53 57 43 37 exact match 99.6% 100% 98.2% 93.0% 100%

within ±1 color block 100% 100% 100% 100% 100%


Urobilinogen REFERENCE: AX-4030 normal 1+ 2+ 3+ 4+

AE-

4022

normal 2009 7 0 0 0 1+ 13 126 1 0 0 2+ 0 13 60 0 0 3+ 0 3 3 37 0 4+ 0 0 0 4 35

total 2022 146 64 41 35 exact match 99.4% 86.3% 93.8% 90.2% 100% within ±1

color block 100% 100% 100% 100% 100%


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pH REFERENCE: AX-4030 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0

AE-

4022

5.0 289 8 0 0 0 0 0 0 0 5.5 30 514 9 0 0 0 0 0 0 6.0 0 44 424 6 0 0 0 0 0 6.5 0 0 63 382 10 0 0 0 0 7.0 0 0 0 12 216 13 0 0 0 7.5 0 0 0 0 10 93 5 0 0 8.0 0 0 0 0 0 18 69 4 0 8.5 0 0 0 0 0 0 3 38 0 9.0 0 0 0 0 0 0 0 14 33

total 319 566 496 400 236 124 77 56 33 exact match 91% 91% 86% 96% 92% 75% 90% 69% 100%

within ±1 color

block 100% 100% 100% 100% 100% 100% 100% 100% 100%


Specific Gravity

REFERENCE: AJ-4270 <1.005 1.010 1.015 1.020 1.025 >1.030

AE-

4022

<1.005 101 5 2 0 0 0 1.010 13 26 13 1 0 0 1.015 0 12 77 31 0 0 1.020 0 0 4 102 1 0 1.025 0 0 0 11 77 0 1.030 0 0 0 0 9 63 total 114 43 96 145 87 63

exact match 89% 60% 80% 70% 89% 100% within ±1

color block 100% 100% 98% 99% 100% 100%


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Blood REFERENCE: AX-4030 neg 1+ 2+ 3+ 4+

AE-

4022

Neg 289 7 0 0 0 1+ 9 48 3 0 0 2+ 2 4 52 1 0 3+ 0 0 7 42 1 4+ 0 0 0 11 72

total 300 59 62 54 73 exact match 96.3% 81.4% 83.9% 77.8% 98.6% within ±1

color block 99.3% 100% 100% 100% 100%

Overall exact agreement = 92% Within +/- 1 block agreement =100%

Ketones REFERENCE: AX-4030 neg ± 1+ 2+ 3+ 4+

AE-

4022

neg 1584 14 0 0 0 0 ± 26 151 12 0 0 0

1+ 0 10 219 13 0 0 2+ 0 0 1 101 8 0 3+ 0 0 0 0 46 4 4+ 0 0 0 0 0 32

total 1610 175 232 114 54 36 exact match 98.4% 86.3% 94.4% 88.6% 85.2% 88.9% within ±1

color block 100% 100% 100% 100% 100% 100%


Nitrites REFERENCE: AX-4030 neg 1+ 2+

AE-

4022

neg 2058 0 0 1+ 12 44 0 2+ 0 3 92

total 2070 47 92 exact match 99.4% 93.6% 100% within ±1

color block 100% 100% 100%


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Leukocytes REFERENCE: AX-4030 neg 25 75 250 500

AE-

4022

Neg 318 5 0 0 0 25 9 34 5 0 0 75 1 5 37 3 0 250 0 0 9 48 1 500 0 0 0 8 65 total 328 44 51 59 66

exact match 96.9% 77.3% 72.6% 81.4% 98.5% within ±1

color block 100% 100% 100% 100% 100%


b. Matrix comparison:

Not applicable. This device is for testing with human urine only.

3. Clinical studies:

a. Clinical Sensitivity:

Not applicable.

b. Clinical specificity:

Not applicable.

c. Other clinical supportive data (when a. and b. are not applicable):

Not applicable.

4. Clinical cut-off:

Not applicable.

5. Expected values/Reference range:

Reference ranges:

Analyte Expected Value Glucose Negative Protein Negative or trace

Bilirubin Negative Urobilinogen 0.2-1mg/dL

pH 4.6-8.0

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Blood Negative Ketones Negative Nitrite Negative

Leukocytes Negative Specific Gravity 1.001-1.035

Literature references are provided to support the stated reference ranges.

1. Brunzel, N.A. Fundamentals of Urine and Body Fluid Analysis. 2nd ed. Philadelphia: Saunders. 2004.

2. Free, A. H., et al. Clinical Chemistry, 1957; 3: 716 3. Henry, J.B. et al. Clinical Diagnosis and Management of Laboratory Methods, 21st

ed. Philadelphia: Saunders; 2007. 4. Tietz Fundamentals of Clinical Chemistry, 4th ed. Philadelphia: Saunders. 1996.

N. Instrument Name:


O. System Descriptions:

1. Modes of Operation:

Does the applicant’s device contain the ability to transmit data to a computer, webserver, or mobile device?

Yes ____X___ or No ________

Does the applicant’s device transmit data to a computer, webserver, or mobile device using wireless transmission?

Yes ________ or No ___X_____

2. Software:

FDA has reviewed applicant’s Hazard Analysis and software development processes for this line of product types:

Yes ___X____ or No ________

3. Specimen Identification:

A patient ID is entered either manually using the keypad or scanned using the barcode reader.

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4. Specimen Sampling and Handling:

The AUTION ELEVEN AE-4022 Semi-automatic Urine Analyzer requires the user to dip an AUTION Stick 10EA test strip into a patient urine specimen of sufficient volume. The user then removes the strip and excess urine, and places the test trip onto the instrument. The remaining operations of the test are carried out automatically. The test strip feeding mechanism transports the test strip to the photometric section of the instrument. After 60 seconds to allow for the analyte reacting with the reagent chemistries, the instrument measures each pad’s reflectance, and converts the reflectance to a qualitative and semi-quantitative result.

5. Calibration:

Calibration of the AUTION Sticks 10EA by the user is not required.

6. Quality Control:

Use of control material is recommended in labeling. Controls should be run: 1) daily, 2) whenever a new bottle of test sticks is opened, 3) before reporting unusual results, and 4) when training new operators.

Control material is not provided with the system. Instead, user manual recommends use of commercially available control material.

P. Other Supportive Instrument Performance Characteristics Data Not Covered In The “Performance Characteristics” Section above:

1. Temperature and Humidity Study:

Temperature and humidity operating conditions of the analyzer were evaluated at temperatures ranging from 8 to 32ºC and relative humidity from 28% to 62%. The conditions included combinations of the lowest humidity and highest temperature. The results support the sponsor’s claimed operating temperature for the AUTION ELEVEN AE-4022 Semi-automatic Urine Analyzer of 10 to 30ºC with relative humidity ranging from 30% to 60%.

2. EMC:

Sponsor provided test reports from independent testing firm demonstrating compliance with the following EMC standards:

UL 61010-1: Electrical Equipment For Measurement, Control, and Laboratory Use; Part 1: General Requirements.

IEC 61010-2-101: Safety requirements for electrical equipment for measurement, control and laboratory use - Part 2-101: Particular requirements for in vitro diagnostic

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(IVD) medical equipment.

CAN/CSA 61010-1-04: Safety Requirements for Electrical Equipment For Measurement, Control, and Laboratory Use; Part 1: General Requirements.

IEC 61010-2-081: Safety requirements for electrical equipment for measurement, control, and laboratory use - Part 2-081: Particular requirements for automatic and semi-automatic laboratory equipment for analysis and other purposes.

FCC Part 15 Radio Frequency Device Subpart B Unintentional Radiators.

Operating mode: During testing, an exercise program was used to run the instrument (included the barcode reader) in a manner similar to typical use.

3. Software:

The software documentation was reviewed and found to be acceptable. The sponsor provided documentation to support that the device was designed, developed and is under good software lifecycle processes.

4. Barcode reader

A hand held barcode reader is optionally available with the AUTION ELEVEN AE-4022 Semi-automatic Urine Analyzer for entering patient IDs. The functional performance of the barcode reader was verified against the design specifications. The manual input of patient ID was compared for data integrity to a scanned barcode input across 5 different test ID’s, and across two different field formats; (1) full 13 numeric characters and (2) 10 numeric characters starting at the second numeric character. The verification test demonstrated that the bar code reader operates as intended to the design specifications.

5. Color tone measurement

The AUTION ELEVEN AE-4022 Semi-automatic Urine Analyzer measures 23 urine color tones. This is done by measuring the reflectance of a blank pad on the AUTION 10EA Stick. The concentration for each analyte is corrected for urine color tone.

Studies were conducted to verify that the system is able to detect a broad range in colors. Because the occurrence of patient samples covering the 23 possible color tones is rare, the samples used in the testing were urine spiked with dyes. Each of 23 different colored samples (yellow, red, green, blue, violet, orange, brown with hues of dark, normal, light) was manually dispensed onto a test strip pad. The reflectance was read and transformed into a color measurement. These results were compared to a visual read. All colors were detected.

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Q. Proposed Labeling:

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

R. Conclusion:

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

510(k) substantial equivalence …5- nitroaniline in acidic medium. varying bilirubin levels will...

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